This proposal studies adrenergic responsiveness in patients with panic disorder, patients with major depression, and normal controls. We will obtain heart rate (HR) and blood pressure (BP) variability measures by Fourier transformation of time series of these signals using noninvasive techniques. HR variability has been extensively used in cardiovascular research to study cardiac autonomic function. Mid Frequency (0.07-0.15 Hz) (MF) power is dually mediated by cholinergic an adrenergic systems while High Frequency (0.2-0.5 Hz) (HF) power is mediated exclusively by cholinergic system. Yohimbine increases the standing MF power while clonidine decreases it. We will use oral doses of clonidine (150 mcg), an alpha-2 adrenoceptor agonist and yohimbine (20 mg), an alpha-2 adrenoceptor antagonist in a placebo-controlled randomized double-blind design to study the effects of these agents on HR and BP variability. We will use standing MF power as a measure of relative adrenergic function and MF/HF ratios to study sympathovagal interaction. We will study 25 panic disorder patients without a current history of major depression, 25 patients with major depression without a history of panic disorder and 25 normal controls using SCID-P for the diagnoses. We will use rating scales for anxiety and panic during the experiments. We will use palsma MHPG levels in supine and standing postures before and after the drug administration, and correlate these measures with anxiety and standing MF power. We hypothesize that patients with panic disorder will have an exaggerated response of standing MF power to yohimbine and clonidine compared to the other two groups. This study will help us examine the specificity of our previous findings of higher relative standing MF power and an exaggerated response to yohimbine of the standing MF power in panic disorder patients. These findings may also enhance our understanding regarding the mechanism of action of certain anti-anxiety agents.